Oleandomycin

687.86

687.86

223-495-7

DTXSID4023389

White, amorphous powder

J - Antiinfectives for systemic use

166 Ų

1.69 (LogP)|log Kow = 1.69

1.21±0.1 g/cm3

110 °C (decomp)

802.6±65.0 °C(Predicted)

Sol in dil acids. Freely sol in methanol, ethanol, butanol, acetone. Practically insol in hexane, carbon tetrachloride, dibutyl ether|In water, 16 mg/L at 25 °C (est)

3.4X10-25 mm Hg at 25 °C (est)

LD50 orl-rat: 6700 mg/kg AMPMAR 39,259,1978

pKa 8.84(H2O,t =25,I=0.167) (Uncertain)

Henry's Law constant = 2.0X10-28 atm-cu m/mole at 25 °C (est)

pKa = 8.84 (tertiary amine)

Long needles from ethyl acetate, mp 134-135 °C. Specific optical rotation = -54 °For D (sodium) line at 25 °C (methanol). Freely sol in water. Forms various cryst hydrates /Hydrochloride/|Mol wt: 785.85 /Phosphate/|Hydroxyl radical reaction rate constant = 2.8xX0-10 cu cm/molecule-sec at 25 °C (est)

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Tolerances are established for negligible residues of oleandomycin in uncooked edible tissues of chickens, turkeys, and swine at 0.15 part per million.|New animal drugs for use in animal feeds. Requirement of a medicated feed mill license. Oleandomycin is included on this list.|New animal drugs for use in animal feeds. ... (1) Chickens and turkeys: Indications for use. For increased rate of weight gain and improved feed efficiency for broiler chickens and growing turkeys. ... (2) Swine: Indications for use. For increased rate of weight gain and improved feed efficiency in growing-finishing swine.|The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Oleandomycin is included on this list.

Macrolide antibiotics probably should not be used with chloramphenicol or the lincosamides because they may compete for the same 50 S ribosomal binding site, although the in vivo significance of this potential interaction is unclear. Activity of macrolides is depressed in acidic environments. Macrolide preparations for parenteral administration are incompatible with many other pharmaceutical preparations. ... /Macrolides/|... /The ability to/ Induce phase III migrating myoelectric complex (MMC) activity in dogs and increase smooth muscle contractility ... is shared to varying extents by some macrolide antibiotics, including oleandomycin ... /Motilin: macrolides and erythromycin/|The combination effect of tetracycline (TC) and oleandomycin (OM) on acute infection of mice with four strains of Staphylococcus aureus including TC or OM resistant ones was examined by the quantitative determination of protective potencies of single and combined drugs. The grade of synergism was expressed by the synergistic ratio (SR), a ratio of experimentally determined potency of the combined drug over a hypothetical potency in which additive effect of the both drugs is assumed. With 3 out of the 4 strains of S. aureus synergism between TC and OM or triacetyloleandomycin (TAO) was demonstrated by the determination of the 50% effective dose and by statistical examination of the SR. The grade of synergistic protection by these drugs varied with the strains infected and it did not depend upon the sensitivity to antibiotics or grade of synergism in vitro. There was no synergistic enhancement of acute toxic action in the combined administration of TC and OM to mice.

Oleandomycin consists of a single component produced by Streptomyces antibioticus(1).

Oleandomycin's production and use as a veterinary antibacterial drug(1,2) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 200(SRC), determined from a log Kow of 1.69(2) and a regression-derived equation(3), indicates that oleandomycin is expected to have moderate mobility in soil(SRC). The pKa of oleandomycin is 8.84(2), indicating that this compound will exist primarily as a cation in the environment, and cations generally have lower mobility in soils than their neutral counterparts(4). Volatilization of oleandomycin from moist soil surfaces is not expected to be an important fate process(SRC) because cations do not volatilize. Biodegradation data were not available(SRC, 2006).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 200(SRC), determined from a log Kow of 1.69(2) and a regression-derived equation(3), indicates that oleandomycin is not expected to adsorb to suspended solids and sediment(SRC). A pKa of 8.84 (tertiary amine)(2) indicates that this compound will exist primarily as a cation in the environment and cations generally adsorb to sediment more strongly than their neutral counterparts(4). Volatilization from water surfaces is not expected(SRC) because cations do not volatilize. According to a classification scheme(5), an estimated BCF of 11(SRC), from an estimated log Kow(2) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data were not available(SRC, 2006).|ATMOSPHERIC FATE: Oleandomycin absorbs light at wavelengths >290 nm (UV max = 286-289 nm(1)) and therefore may be susceptible to direct photolysis by sunlight(2).

Oleandomycin contains hydrolyzable functional groups and therefore may undergo hydrolysis in the environment(1); however, a rate constant could not be estimated for this structure. Oleandomycin absorbs light at wavelengths >290 nm (UV max = 286-289 nm(2)) and therefore may be susceptible to direct photolysis by sunlight(1).

An estimated BCF of 11 was calculated for oleandomycin(SRC), using a log Kow of 1.69(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Koc of oleandomycin is estimated as 200(SRC), using a log Kow of 1.69(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that oleandomycin is expected to have moderate mobility in soil. The pKa of oleandomycin is 8.84 (tertiary amine)(1), indicating that this compound will exist primarily as a cation in the environment, and cations generally have lower mobility in soils than their neutral counterparts(4).

A measured pKa of 8.84 (tertiary amine)(1) indicates that oleandomycin will exist primarily as a cation in the environment. Volatilization of oleandomycin from moist soil or water surfaces is not expected to be an important fate process(SRC) since cations do not volatilize.

Occupational exposure to oleandomycin may occur through dermal contact with this compound at workplaces where oleandomycin is produced or used. Exposure to oleandomycin among the general population may be limited to those who administer this substance to animals. (SRC)

Mesh Heading: anti-bacterial agents|MEDICATION: ... Used orally or intravenously to treat pyoderma, sepsis, meningitis, surgical and abdominal infections, respiratory tract and urinary tract infections, and other infections caused by Staphylococci, Streptococci, Corynebacterium, Neisseria, and Mycoplasma.|MEDICATION (VET): Macrolide antibiotic.|THERAP CAT: Antibacterial|For more Therapeutic Uses (Complete) data for OLEANDOMYCIN (6 total), please visit the HSDB record page.

VET: Toxicity and side effects are uncommon for most macrolides ... , although pain and swelling may develop at injection sites. Hypersensitivity reactions have occasionally been seen. ... Horses are sensitive to macrolide-induced CI disturbances that can be serious and even fatal. ...

Macrolides become widely distributed in tissues, and concentrations are about the same as in plasma, or even higher in some instances. They actually accumulate within many cells, including macrophages, in which they may be > or = 20 times the plasma concentration. This accumulation accounts in part for the long dosing interval that characterizes some macrolides (eg, tilmicosin). ... Macrolides tend to concentrate in the spleen, liver, kidneys, and particularly the lungs. They enter pleural and ascitic fluids but not the CSF (only 2-13% of plasma concentration unless the meninges are inflamed). They concentrate in the bile and milk. Up to 75% of the dose is bound to plasma proteins, and they bind to alpha1-acid glycoproteins rather than to albumin. /Macrolides/|Macrolides are readily absorbed from the GI tract if not inactivated by gastric acid. ... Plasma levels peak within 1-2 hours in most cases, although absorption patterns may be erratic due to the presence of food and may depend on the salt or ester used. Absorption from the ruminoreticulum is usualy delayed and is unreliable. /Macrolides/|Macrolide antibiotics and their metabolites are excreted mainly in the bile (> 60%) and often undergo enterohepatic cycling. Urinary clearance may be slow and variable (often <10%) but my represent a more significant route of elimination after parenteral administration. The concentration of macrolides in milk often is several times greater than in plasma, especially in mastitis. /Macrolide/|The pharmacokinetics of oleandomycin (OLD) after intravenous and oral administration, both alone and after intramuscular pretreatment with metamizole or dexamethasone, were studied in healthy dogs. After intravenous injection of oleandomycin alone (10 mg/kg as bolus), the elimination half-life (t 1/2 beta, volume of distribution (Vd, area), body clearance (ClB) and area under the concentration time curve (AUC) were 1.60 hr, 1.11 L/kg. 7.36 (ml/kg)/min and 21.66 ug hr/ml, respectively. There were no statistically significant differences following pretreatment with metamizole or dexamethasone. After oral administration of oleandomycin alone, the t 1/2 beta, maximum plasma concentrations (Cmax), time of Cmax (tmax), mean absorption time and absolute bioavailability (Fabs) were 1.6 hr, 5.34 ug/ml, 1.5 hr, 1.34 hr and 84.29%, respectively. Pretreatment with metamizole caused a significantly decreased value for Cmax (2.93 ug/ml) but the mean absorption time value (2.23 hr) was significantly increased. Statistically significant changes in the pharmacokinetic parameters of oleandomycin following oral administration were also observed as a result of pretreatment with dexamethasone. The Cmax was increased (8.24 ug/ml) and the tmax (0.5 hr) and mean absorption time (0.45 hr) were lower.|Knowledge of the disposition of macrolides in a single animal species has been insufficient for the prediction of the pharmacokinetics of macrolides in humans. To better understand the species differences in the pharmacokinetics of macrolide antibiotics, the disposition of erythromycin, oleandomycin, and tylosin in several mammalian species was examined. Generally, the serum concentration versus time profiles of these drugs after intravenous administration were described by two-compartment kinetic models and were similar within each species. These drugs were rapidly cleared, resulting in terminal half-lives of less than 2 h. Comparison of their pharmacokinetics showed greater variation in antibiotic disposition among animal species than noted for the differences within a species. When the pharmacokinetic data was fitted to an allometric model, the logarithms of volume of distribution, clearance, and half-life were linearly related to the logarithms of body weight. From these relationships, the human pharmacokinetics of erythromycin and oleandomycin were extrapolated and found to approximate observed human pharmacokinetics.

Metabolic inactivation of the macrolides is usually extensive, but the relative proportion depends on the route of administration and th particular antibiotic. ... /Macrolides/

The plasma half-lives of macrolides usually are 1-3 hr, ... /Macrolides/

The antimicrobial mechanism seems to be the same for all of the macrolides. They interfere with protein synthesis by reversibly binding to the 50 S subunit of the ribosome. They appear to bind at the donor site, thus preventing the translocation necessary to keep the peptide chain growing. The effect is essentially confined to rapidly dividing bacteria and mycoplasmas. Macrolides are regarded as being bacteriostatic, ... . Macrolides are significantly more active at higher pH ranges (7.8-8). /Macrolides/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

Analyte: oleandomycin; matrix: blood (plasma), tissue (liver); procedure: high-performance liquid chromatography with electrochemical (amperometric) detection

Veterinary Drug -> ANTIMICROBIAL_AGENT; -> JECFA Functional Classes

Veterinary Drug -> ANTIMICROBIAL_AGENT;